Plasma protein corona on silica nanoparticles enhances exocytosis

While the influence of the protein corona on nanoparticle uptake in mammalian cells is well understood, little is known about the influence of the protein corona on nanoparticle exocytosis. However, the exocytosis of nanoparticles also contributes to the therapeutic efficacy as it influences the net delivery of nanoparticles to a cell. In this study we demonstrate that the exocytosis of silica nanoparticles from HCT 116 cells is enhanced by the pre-adsorption of a human plasma protein corona. This pre-adsorption effect also depends on the diameter of the nanoparticles. The exocytosis of small silica nanoparticles (10 nm) is less pronounced, while the exocytosis of larger silica nanoparticles (100 nm) is significantly increased in the presence of a protein corona. A proteomic analysis of the plasma protein corona of the different-sized silica nanoparticles (10 nm, 30 nm, 50 nm, and 100 nm) reveals different protein compositions. Apolipoproteins and coagulation proteins are enriched in a size-dependent manner with high amounts of apolipoproteins adsorbed to small silica nanoparticles. The findings underscore the significance of the nanoparticle protein corona for exocytosis and demonstrate the need to engineer nanocarriers that are not exocytosed rapidly to enhance the efficacy in drug delivery.